# Study of ANP Receptor:Gene Targeting and Expression

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2020 · $376,250

## Abstract

PROJECT SUMMARY
The mechanisms regulating blood pressure are known to have strong genetic components; however, the
specific genes involved in the pathogenesis of hypertension are not well defined. Key regulators are atrial and
brain natriuretic peptides (ANP, BNP) signaling through their cognate natriuretic peptide receptor-A (NPRA)
and the second messenger cGMP. The ANP-BNP/NPRA system plays critical roles in the regulation of blood
pressure and reno-vascular homeostasis. There is a strong association of polymorphisms in the genes that
encode ANP (Nppa), BNP (Nppb), and NPRA (Npr1) with high blood pressure and cardiovascular dysfunction
in humans. These phenotypes can be recapitulated using global Npr1 gene-knockout system in mice. Both
male and female mice lacking global Npr1 gene (Npr1-/-) exhibit high blood pressure, but specifically male Npr1
mice suffer from hypertension, heart failure, and sudden death at adult age. It is not clear how the lack of
Npr1 in the specific cell-types of kidneys and vasculature progressively leads to hypertension, nor what
underlies the observed sex-differences in the global Npr1-/- mice. The Npr1 deletion exhibiting malignant
hypertension in mice is significant and complements clinical findings of polymorphisms in Nppa, Nppb, and
Npr1 in humans. The mechanistic understanding of how the absence of Npr1 divergently affects blood
pressure in a sex-related manner remains an important yet unanswered question. We hypothesize that cell-
specific deletion of Npr1 plays critical roles in the development of molecular and cellular perturbations of
immunogenic and inflammatory mechanisms leading to activation of Toll-like receptors (TLRs), redox-sensitive
transcription factor nuclear factor kappa B (NF-κB), adaptive T cells, and macrophages. The long-term goal of
this proposal is to determine the molecular and genetic factors that contribute to immunogenic chronic
inflammation leading to hypertension and reno-vascular dysfunction. The overall objective of the proposed
studies is to determine the mechanistic aspects of the loss of nephron tubules (NT)- and vascular smooth
muscle cell (SMC)-specific Npr1, leading to hypertension and reno-vascular remodeling and dysfunction. The
central hypothesis is that the cell-specific loss of Npr1 in the kidneys and vasculature triggers the
immunogenic and inflammatory processes that provoke hypertension and end-organ damage in a sex-
dependent manner. The proposed specific aims will test the hypotheses: 1) the damage-associated immune
receptors contribute to hypertension and reno-vascular dysfunction; 2) the down-stream redox-sensitive
cascades trigger high blood pressure and renal-vascular injury and dysfunction; and 3) immunogenic
mechanisms provoke hypertension, and renal-vascular disorders. The successful completion of the proposed
studies could lead to the identification of much-needed new biomarkers and therapies for the treatment and
prevention of hypertension and renal-vascular ...

## Key facts

- **NIH application ID:** 9930111
- **Project number:** 5R01HL062147-19
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Kailash N Pandey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $376,250
- **Award type:** 5
- **Project period:** 1998-06-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930111

## Citation

> US National Institutes of Health, RePORTER application 9930111, Study of ANP Receptor:Gene Targeting and Expression (5R01HL062147-19). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9930111. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*